The evolution of sociality is difficult to explain because social systems involve cooperative selfless behaviors, which are seemingly inconsistent with natural selection, but kin selection theory explains that natural selection would favor cooperation when relatedness exceeds the cost to benefit ratio. Some of the outstanding questions in the field are how organisms recognize each other as kin, how does kin-recognition evolve, and whether kin-recognition is indeed a mechanism that facilitates the evolution of sociality. Answering these questions in a genetically tractable system is a considerable challenge in the field. We have discovered a kin-recognition mechanism, which is mediated by a pair of polymorphic cell-cell adhesion proteins in the social amoeba Dictyostelium discoideum. We have also discovered dozens of mutants that cheat through various molecular mechanisms. Here we propose to study the role of kin-recognition in protection against cheating and the mechanisms that allow kin-recognition itself to evolve. We will first test the hypothesis that kin-recognition can protect sociality against various cheaters (Aim 1). We will then test whether allele duplication and diversification could be part of a mechanism that allows kin-recognition to evolve (Aim 2) and whether it may explain how rare social cues evolve and become established (Aim 3). It is becoming increasingly evident that pathogenesis of microbes, such as bacteria, yeast and amoebae, is affected by microbial social behavior. Moreover, natural mechanisms of resistance to microbes, such as the immune system, and medical interventions, such as antibiotic treatment, have profound effects on the evolution of sociality in microbial pathogens. Studying the evolution of microbial sociality is therefore central to understanding and treating microbial pathogenesis. PUBLIC HEALTH RELEVANCE: It is becoming increasingly evident that pathogenesis of microbes, such as bacteria, yeast and amoebae, is affected by microbial social behavior. Moreover, natural mechanisms of resistance to microbes, such as the immune system, and medical interventions, such as antibiotic treatment, have profound effects on the evolution of sociality in microbial pathogens. Studying the evolution of microbial sociality is therefore centra to understanding and treating microbial pathogenesis, hence its importance to public health.